(With Regard to Cancer Prevention)
Since cancer became a major cause of death, various attempts have been made to elucidate risk factors and inhibitory factors for cancer development so as to utilize these factors in cancer prevention through elimination or ingestion thereof, as well as to develop drugs for treatment of cancer. As typical examples of the risk factors for cancer development, there are known a lifestyle such as smoking, and persistent infection with a hepatitis virus (hepatoma), a parvovirus (cervical cancer), Helicobacter pylori (gastric cancer), or the like. As an example of the utilization of the elimination of the risk factors in cancer prevention, there is given a preventive vaccine therapy for blocking infection with a hepatitis B virus and a parvovirus.
On the other hand, for the inhibitory factors, large-scale epidemiological investigations have been performed on foods. Further, in drugs, it has been reported that a non-steroidal anti-inflammatory drug for large bowel cancer or a selective estrogen receptor modulator (SERM) for breast cancer reduces a risk of cancer development.
Possible mechanisms of cancer prevention with the foods or the drugs are proliferation inhibition of cancer cells, apoptosis induction, modification of a hormone receptor, an increase in immune sensitivity of cancer cells, and the like.
A concept of such cancer prevention is based on the following perspective: how to inhibit factors on the cancer cell side, such as transformation from normal cells to cancer cells and proliferation and metastasis of cancer cells. On the other hand, it is also theoretically possible to inhibit cancer development by enhancing factors on the living body side for protecting against the cancer development, that is, immune surveillance abilities as described below from a tumor immunological viewpoint.
(With Regard to Immune System)
In the middle of the 20th century, Burnet proposed, based on experiments using mice, the presence of an immune surveillance mechanism in which precancerous cells were recognized and eliminated by the immune system to block their progression to cancer, thereby maintaining homeostasis of an individual. After that, evidence of the presence of the immune surveillance mechanism was demonstrated by development of genetically-modified mouse models, and complicated associations and processes between the cancer development and the immune system were organized in the immunoediting theory by Dunn et al. (Non Patent Literature 1: Nat. Immunl. 2002; 3: 991).
According to the immunoediting theory, the processes to cancer development are divided into three stages, i.e., elimination, equilibrium, and escape. In particular, the first stage, i.e., elimination has substantially the same meaning as the immune surveillance theory, and is a process in which initial cancer cells are eliminated before formation of a large population. In the first half of this process, NK cells, NKT cells, γδT cells, macrophages, and dendritic cells as innate immune cells function in cooperation with each other to eliminate tumor cells. In the second half, the dendritic cells present cancer antigens to T cells to produce clones of cancer antigen-specific helper T cells and cytotoxic T cells, and acquired immunity functions so as to eliminate cancer cells that have not been able to be eliminated by innate immunity alone.
At the second stage, i.e., equilibrium, selection of cancer cells having low immunogenicity progresses even in a living body retaining normal immune functions. Finally, the cancer cells acquire immune resistance, and proliferation of the cancer cells gradually occurs.
The third stage, i.e., escape is a stage at which the immune system cannot recognize cancer cells any more, which causes a rapid increase in cancer tissue, with the result that cancer is clinically detectable.
As the stage becomes more advanced from the equilibrium, it becomes more difficult to inhibit progression of cancer. Hence, in order to inhibit cancer development, it is essential to certainly eliminate cancer cells at the first stage, i.e., elimination. However, functions of innate immune cells and acquired immune cells are reduced by aging, stress, and the like, with the result that their abilities to eliminate cancer cells are not sufficiently exhibited. For example, although cytotoxicity and interferon-γ productivity of NK cells are also attenuated by aging, there is a report that functions of NK cells and NKT cells in the innate immune system are kept high in immune abilities of centenarians (Non Patent Literature 2: J. Clin. Immunol. 2009; 29: 416).
(Means for Inhibiting Cancer Development)
The previously reported means for inhibiting cancer development are limited to a food, a supplement (e.g., selenium or a vitamin), an anti-inflammatory drug, and a selective estrogen receptor modulator (SERM), all of which directly act on cancer cells to inhibit their progression, and the inhibiting effects are not necessarily high. Further, as a countermeasure for attenuation of a vaccine effect by aging and the like, it is only possible to increase a single dosage of a vaccine adjuvant or a vaccine or the number of times of administration.
(With Regard to Hepatitis)
In the world, there are 360,000,000 chronic hepatitis patients infected with a hepatitis B virus who are at risk of developing liver cirrhosis and hepatoma. This has become a big issue. Although attempts to use a hepatitis B vaccine for preventive uses as a vaccine for “treatment” of chronic hepatitis B in combination with a virus proliferation inhibitor were made, no satisfactory clinical improvement was found (Non Patent Literature 3: Vaccine 2007; 25: 8585 and Non Patent Literature 4: Hepat. Res. Treat. 2010; 2010: 817580).
In addition, development of a “treatment” vaccine therapy has also been explored, such as a clinical trial on a novel DNA vaccine (Non Patent Literature 5: Gene Ther. 2006; 13: 1110) or immune complex vaccine (Non Patent Literature 6: PLoS One 2008; 3: e2565).
However, the presence of a population (e.g., males aged 60 or more) showing no or very little increase in antibody titer even when a general HB vaccine is administered has become an issue.
In addition, interferon to be generally used in treatment of hepatitis exhibits different therapeutic effects depending on patients. Thus, there is a need for establishment of a novel treatment method.
(With Regard to Agent for Improvement of Antibody Production)
There are reports on agents for improvement of antibody production.
In Patent Literature 1, there is a disclosure of an “agent for induction of antibody production, including a tea polysaccharide as an active ingredient.”
In Patent Literature 2, there is a disclosure of an “agent for improvement of antibody productivity of a vaccine, characterized by containing egg white.”
However, none of the literatures discloses or suggests an “agent for improvement of antibody production, including NK cells.” In addition, there are many reports that the NK cells inhibit antibody productivity (Non Patent Literature 7: Cell. Immunol. 1995; 161: 42). That is, in the conventional findings, it has generally been recognized that the NK cells inhibit antibody productivity.